Wound healing in mice with high-fat diet- or ob gene-induced diabetes-obesity syndromes: a comparative study.

Wound healing in mice with high-fat diet- or ob gene-induced diabetes-obesity syndromes: a comparative study.
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DOI:
10.1155/2010/476969
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发表时间:
2010
影响因子:
--
通讯作者:
Goren I
Goren I
中科院分区:
其他
文献类型:
--
作者:
Seitz O;Schürmann C;Hermes N;Müller E;Pfeilschifter J;Frank S;Goren I

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在过去,遗传性糖尿病-肥胖糖尿病/糖尿病(db/db)和肥胖/肥胖(ob/ob)小鼠品系被用于研究糖尿病损害伤口愈合的机制。在这里,我们确定了遗传正常的C57 Bl/6 J小鼠的皮肤修复模式,这些小鼠用高脂饮食(HFD)喂养以诱导糖尿病-肥胖综合征。与接受标准饲料(CD)的小鼠相比,HFD喂养的小鼠的伤口闭合明显延迟。HFD小鼠受损的伤口组织显示伤口炎症的显著延长。血管内皮生长因子(VEGF)的表达延迟,并与伤口边缘上皮细胞的干扰形成和减少肉芽组织中血管生成受损相关。正常的伤口收缩被延迟和紊乱。肥胖C57 Bl/6 J小鼠的创伤疾病是由于NFκB抑制剂(IκB-α)在缺乏Akt活化的情况下显著降解所致。与ob/ob小鼠受损的伤口状况相反,HFD小鼠的晚期伤口没有出现慢性炎症状态,并且在修复11天后就形成了上皮。因此,只有遗传性肥胖和糖尿病ob/ob小鼠最终形成慢性伤口,因此代表了更适合研究糖尿病诱导的伤口愈合障碍的实验模型。
In the past, the genetically diabetic-obese diabetes/diabetes (db/db) and obese/obese (ob/ob) mouse strains were used to investigate mechanisms of diabetes-impaired wound healing. Here we determined patterns of skin repair in genetically normal C57Bl/6J mice that were fed using a high fat diet (HFD) to induce a diabetes-obesity syndrome. Wound closure was markedly delayed in HFD-fed mice compared to mice which had received a standard chow diet (CD). Impaired wound tissue of HFD mice showed a marked prolongation of wound inflammation. Expression of vascular endothelial growth factor (VEGF) was delayed and associated with the disturbed formation of wound margin epithelia and an impaired angiogenesis in the reduced granulation tissue. Normal wound contraction was retarded and disordered. Wound disorders in obese C57Bl/6J mice were paralleled by a prominent degradation of the inhibitor of NFκB (IκB-α) in the absence of an Akt activation. By contrast to impaired wound conditions in ob/ob mice, late wounds of HFD mice did not develop a chronic inflammatory state and were epithelialized after 11 days of repair. Thus, only genetically obese and diabetic ob/ob mice finally developed chronic wounds and therefore represent a better suited experimental model to investigate diabetes-induced wound healing disorders.
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